During early development, the inactivation of one X chromosome in female mammals ensures equivalent X-linked gene expression in male (XY) and female(XX) embryos. X-inactivation is triggered by the association of non-coding Xist (X-inactive specific transcript) RNA with one X chromosome. In ES cells, the conserved A-repeat of the Xist RNA is then required to silence that chromosome. Now, on p. 139, Hoki and colleagues report that the A-repeat is also required for X-inactivation during mouse embryogenesis. Surprisingly, however, a lack of Xist RNA,rather than defective silencing by the mutated RNA, causes the failure of imprinted X-inactivation (the inactivation of the paternal X in the extraembryonic tissues) in embryos carrying a paternally transmitted A-repeat-deleted Xist allele. Furthermore, the normally silent paternal copy of Tsix (a negative regulator of Xist) is ectopically activated in these A-repeat-deleted embryos. The researchers suggest, therefore, that the genomic region encoding the A-repeat is required for the appropriate transcriptional regulation of the Xist/Tsix loci and subsequent X-inactivation in mouse embryos.